23848-46-6Relevant academic research and scientific papers
Specific Interactions between Sodium Deoxycholate and its Water-Insoluble Analogues. Mechanisms for Premicelle and Micelle Formation of Sodium Deoxycholate
Kano, Koji,Tatemoto, Shinichi,Hashimoto, Shizunobu
, p. 966 - 970 (1991)
Interactions between sodium deoxycholate (NaDC, host) and its water-insoluble analogues (guests) have been studied in water (pH 10) to clarify the mechanisms for the premicelle and micelle formation of NaDC.Turbidity measurements have been used as a convenient method to study the interactions between the guest and host molecules.At least two α-hydroxy groups attached to the C-3 and C-12 positions of a steroid nucleus are required for the guest steroids to interact with NaDC below the critical micelle concentration.This strongly suggests the formation of a hydrogen-bonded dimer of NaDC as a premicelle whose formation is assisted by the hydrophobic environment provided by the α-plane of the steroid.The guest steroids having a hydroxy group at the C-3 position and a polar head group at the C-24 position, which can participate in hydrogen bonding, are solubilized by the NaDC micelles.The results support the mechanism for the NaDC micelle formation involving hydrogen bonding between the C-3 hydroxy group of a premicelle and the C-24 carboxylate anion of another premicelle.
Synthesis and characterization of new impurities in obeticholic acid
Feng, Wei-Dong,Zhuo, Song-Ming,Zhang, Fu-Li
, p. 522 - 530 (2019/11/29)
Novel and efficient synthetic strategies are developed for the first synthesis of two new impurities found in obeticholic acid. The synthetic routes to the impurities are designed without column purification using 4-nitrobenzoyl chloride as a selective pr
Rapid Deoxyfluorination of Alcohols with N-Tosyl-4-chlorobenzenesulfonimidoyl Fluoride (SulfoxFluor) at Room Temperature
Guo, Junkai,Kuang, Cuiwen,Rong, Jian,Li, Lingchun,Ni, Chuanfa,Hu, Jinbo
supporting information, p. 7259 - 7264 (2019/05/10)
The deoxyfluorination of alcohols is a fundamentally important approach to access alkyl fluorides, and thus the development of shelf-stable, easy-to-handle, fluorine-economical, and highly selective deoxyfluorination reagents is highly desired. This work describes the development of a crystalline compound, N-tosyl-4-chlorobenzenesulfonimidoyl fluoride (SulfoxFluor), as a novel deoxyfluorination reagent that possesses all of the aforementioned merits, which is rare in the arena of deoxyfluorination. Endowed by the multi-dimensional modulating ability of the sulfonimidoyl group, SulfoxFluor is superior to 2-pyridinesulfonyl fluoride (PyFluor) in fluorination rate, and is also superior to perfluorobutanesulfonyl fluoride (PBSF) in fluorine-economy. Its reaction with alcohols not only tolerates a wide range of functionalities including the more sterically hindered alcoholic hydroxyl groups, but also exhibits high fluorination/elimination selectivity. Because SulfoxFluor can be easily prepared from inexpensive materials and can be safely handled without special techniques, it promises to serve as a practical deoxyfluorination reagent for the synthesis of various alkyl fluorides.
Design, synthesis, and biological evaluation of potent dual agonists of nuclear and membrane bile acid receptors
D'Amore, Claudio,Di Leva, Francesco Saverio,Sepe, Valentina,Renga, Barbara,Del Gaudio, Chiara,D'Auria, Maria Valeria,Zampella, Angela,Fiorucci, Stefano,Limongelli, Vittorio
, p. 937 - 954 (2014/03/21)
Bile acids exert genomic and nongenomic effects by interacting with membrane G-protein-coupled receptors, including the bile acid receptor GP-BAR1, and nuclear receptors, such as the farnesoid X receptor (FXR). These receptors regulate overlapping metabolic functions; thus, GP-BAR1/FXR dual agonists, by enhancing the biological response, represent an innovative strategy for the treatment of enteroendocrine disorders. Here, we report the design, total synthesis, and in vitro/in vivo pharmacological evaluation of a new generation of dual bile acid receptor agonists, with the most potent compound, 19, showing promising pharmacological profiles. We show that compound 19 activates GP-BAR1, FXR, and FXR regulated genes in the liver, increases the intracellular concentration of cAMP, and stimulates the release of the potent insulinotropic hormone GLP-1, resulting in a promising drug candidate for the treatment of metabolic disorders. We also elucidate the binding mode of the most potent dual agonists in the two receptors through a series of computations providing the molecular basis for dual GP-BAR1/FXR agonism.
Modification on ursodeoxycholic acid (UDCA) scaffold. Discovery of bile acid derivatives as selective agonists of cell-surface G-protein coupled bile acid receptor 1 (GP-BAR1)
Sepe, Valentina,Renga, Barbara,Festa, Carmen,Damore, Claudio,Masullo, Dario,Cipriani, Sabrina,Di Leva, Francesco Saverio,Monti, Maria Chiara,Novellino, Ettore,Limongelli, Vittorio,Zampella, Angela,Fiorucci, Stefano
, p. 7687 - 7701 (2014/12/12)
Bile acids are signaling molecules interacting with the nuclear receptor FXR and the G-protein coupled receptor 1 (GP-BAR1/TGR5). GP-BAR1 is a promising pharmacological target for the treatment of steatohepatitis, type 2 diabetes, and obesity. Endogenous bile acids and currently available semisynthetic bile acids are poorly selective toward GP-BAR1 and FXR. Thus, in the present study we have investigated around the structure of UDCA, a clinically used bile acid devoid of FXR agonist activity, to develop a large family of side chain modified 3,7 dihydroxyl cholanoids that selectively activate GP-BAR1. In vivo and in vitro pharmacological evaluation demonstrated that administration of compound 16 selectively increases the expression of pro-glucagon 1, a GP-BAR1 target, in the small intestine, while it had no effect on FXR target genes in the liver. Further, compound 16 results in a significant reshaping of bile acid pool in a rodent model of cholestasis. These data demonstrate that UDCA is a useful scaffold to generate novel and selective steroidal ligands for GP-BAR1.
Synthesis and antitumor activity of N-sulfonyl-3,7-dioxo-5β-cholan-24- amides, ursodeoxycholic acid derivatives
Ren, Jie,Wang, Yongchao,Wang, Junliang,Lin, Jun,Wei, Kun,Huang, Rong
, p. 53 - 58 (2013/02/22)
A series of N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, ursodeoxycholic acid derivatives, have been designed and synthesized in nine steps starting from ursodeoxycholic acid. The in vitro antitumor activity of the target compounds has been evaluated against HCT-116, MCF-7, K562, and SGC-7901 cell lines. The pharmacological results showed that most of the prepared compounds display excellent selective cytotoxicity toward HCT-116, MCF-7, and K562 cell lines. Particularly, compounds 10c, 10f and 10g show high inhibitory activity on these human cancer cell lines (IC50: 2.39-9.34 μM). Conversely, all compounds are generally inactive against SGC-7901, with only 10b having IC50 below 50 μM.
Electron transfer reduction of carboxylic acids using SmI 2-H2O-Et3N
Szostak, Michal,Spain, Malcolm,Procter, David J.
supporting information; experimental part, p. 840 - 843 (2012/04/11)
The first general method for efficient electron transfer reduction of carboxylic acids has been developed. The protocol using SmI2 - H 2O - Et3N allows for reduction of a variety of carboxylic acids in excellent yields and provides an attractive alternative to processes mediated by reactive alkali metals, lithium aluminum hydride, and boron hydrides. Of broader significance, the method allows acyl radical equivalents to be generated from carboxylic acids under mild reaction conditions.
Bile acid toxicity structure-activity relationships: Correlations between cell viability and lipophilicity in a panel of new and known bile acids using an oesophageal cell line (HET-1A)
Sharma, Ruchika,Majer, Ferenc,Peta, Vijaya Kumar,Wang, Jun,Keaveney, Ray,Kelleher, Dermot,Long, Aideen,Gilmer, John F.
body text, p. 6886 - 6895 (2010/10/19)
The molecular mechanisms and interactions underlying bile acid cytotoxicity are important to understand for intestinal and hepatic disease treatment and prevention and the design of bile acid-based therapeutics. Bile acid lipophilicity is believed to be an important cytotoxicity determinant but the relationship is not well characterized. In this study we prepared new azido and other lipophilic BAs and altogether assembled a panel of 37 BAs with good dispersion in lipophilicity as reflected in RPTLC RMw. The MTT cell viability assay was used to assess cytotoxicity over 24 h in the HET-1A cell line (oesophageal). RMw values inversely correlated with cell viability for the whole set (r2 = 0.6) but this became more significant when non-acid compounds were excluded (r2 = 0.82, n = 29). The association in more homologous subgroups was stronger still (r 2 >0.96). None of the polar compounds were cytotoxic at 500 μM, however, not all lipophilic BAs were cytotoxic. Notably, apart from the UDCA primary amide, lipophilic neutral derivatives of UDCA were not cytotoxic. Finally, CDCA, DCA and LagoDCA were prominent outliers being more toxic than predicted by RMw. In a hepatic carcinoma line, lipophilicity did not correlate with toxicity except for the common naturally occurring bile acids and their conjugates. There were other significant differences in toxicity between the two cell lines that suggest a possible basis for selective cytotoxicity. The study shows: (i) azido substitution in BAs imparts lipophilicity and toxicity depending on orientation and ionizability; (ii) there is an inverse correlation between RMw and toxicity that has good predictive value in homologous sets; (iii) lipophilicity is a necessary but apparently not sufficient characteristic for BA cytocidal activity to which it appears to be indirectly related.
Imprinted polymers as protecting groups for regioselective modification of polyfunctional substrates
Alexander, Cameron,Smith, Craig R.,Whitcombe, Michael J.,Vulfson, Evgeny N.
, p. 6640 - 6651 (2007/10/03)
Imprinted polymers were prepared using a functional monomer derived from boronophthalide and a number of steroid templates bearing spatially separated hydroxyl groups. The cooperative nature of the binding interaction was demonstrated in polymers imprinted with androst-5-ene-3β,17β-diol and its structural analogues. The stoichiometry and kinetics of binding were probed using IR spectroscopy, selective solvent extractions, and chemical modification experiments. The feasibility of using imprinted polymers as reusable protecting groups was established by the regioselective acylation of trihydroxysteroids bound to polymers imprinted with structurally related diols. In polymers prepared with tert-butyl ester templates "matched" to the substrate, regioselectivities as high as 23.1:1 (24-acetate:3-acetate) in the monoester products (65% of recovered material) were seen. In the "unmatched" case, the ratio fell to 5.4:1; however, in functionally identical control polymers, imprinted with ethylene glycol, the regioselectivity was completely reversed (1:100), and only poor yields of monoesters (13%) were obtained.
Anti-fungal compounds
-
, (2008/06/13)
Compounds of the general formula (7): STR1 wherein X is a hydrogen atom or a hydroxyl group, Y is a hydrogen atom or a hydroxyl group and at least one of X and Y is a hydroxyl group and Z is a hydroxyl group or a methylol (--CH2 OH) group, have anti-fungal activity, especially against organisms selected from Candida spp. and the athlete's foot/ringworm organisms Trichophyton mentagrophytes and Microsporum audonii. Compounds in which Z is a methylol (--CH2 OH) group are claimed per se.
